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Olaparib Treatment in Relapsed Germline Breast Cancer Susceptibility Gene (BRCA) Mutated Ovarian Cancer Patients Who Have Progressed at Least 6 Months After Last Platinum Treatment and Have Received at Least 2 Prior Platinum Treatments (SOLO3)

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ClinicalTrials.gov Identifier: NCT02282020
Recruitment Status : Active, not recruiting
First Posted : November 4, 2014
Results First Posted : December 2, 2019
Last Update Posted : December 2, 2019
Sponsor:
Collaborators:
Myriad Genetic Laboratories, Inc.
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
AstraZeneca

Tracking Information
First Submitted Date  ICMJE October 20, 2014
First Posted Date  ICMJE November 4, 2014
Results First Submitted Date  ICMJE October 3, 2019
Results First Posted Date  ICMJE December 2, 2019
Last Update Posted Date December 2, 2019
Actual Study Start Date  ICMJE February 6, 2015
Actual Primary Completion Date October 10, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 27, 2019)
Objective Response Rate (ORR) [ Time Frame: Maximum of 45 Months ]
Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria was used by a Blinded Independent Central Review (BICR) to assess participant response to treatment Objective Response Rate (ORR) is the number of participants with Complete Response (CR) or Partial Response (PR) in the Measurable Disease Analysis Set (MDAS). Complete response is declared when all lesions have disappeared or all lesions have disappeared and all nodal disease is < 10 mm each. Partial response is declared when there is a decrease in sum of diameters of target lesions ≥ 30%.
Original Primary Outcome Measures  ICMJE
 (submitted: October 31, 2014)
Progression Free Survival (PFS) by blinded independent central review using Response Evaluation Criteria In Solid Tumours (RECIST) data [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months ]
To determine the efficacy of olaparib vs. physician's choice single agent chemotherapy by assessment of PFS using blinded independent central review
Change History Complete list of historical versions of study NCT02282020 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 27, 2019)
  • Progression Free Survival (PFS) [ Time Frame: Maximum of 45 Months ]
    RECIST 1.1 criteria was used to assess participant response to treatment. PFS was defined as the time from randomization until the date of objective radiological disease progression according to RECIST 1.1 or death (by any cause in the absence of disease progression) regardless of whether the participant withdrew from randomized therapy or received another anti-cancer therapy prior to disease progression (i.e., date of RECIST progression/death or censoring - date of randomization +1).
  • Time From Randomisation to Second Progression (PFS2) [ Time Frame: Maximum of 45 Months ]
    Time from randomization to PFS2 was defined as the time from the date of randomization to the earliest of the progression events subsequent to first progression or death. The date of second progression was recorded by the investigator and defined according to local standard clinical practice, and could involve objective radiological, clinical, cancer antigen-125 (CA-125) progression or death. CA-125 progression was assessed per Gynecological Cancer Intergroup (GCIG) criteria.
  • Overall Survival (OS) [ Time Frame: Maximum of 45 Months ]
  • Time To Earliest Progression By RECIST 1.1 Or Cancer Antigen (CA) -125 Or Death [ Time Frame: Maximum of 45 Months ]
    Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria was used to assess participant response to treatment. CA-125 progression was assessed per Gynecological Cancer Intergroup (GCIG).
  • Time From Randomization To First Subsequent Therapy Or Death (TFST) [ Time Frame: Maximum of 45 Months ]
    TFST was defined as the time from the date of randomization to the earlier of first subsequent therapy start date or death.
  • Time From Randomization To Second Subsequent Therapy Or Death (TSST) [ Time Frame: Maximum of 45 Months ]
    TSST was defined as the time from the date of randomization to the earlier of second subsequent chemotherapy start date following study treatment discontinuation, or death.
  • Time From Randomization To Study Treatment Discontinuation Or Death (TDT) [ Time Frame: Maximum of 45 Months ]
    TDT was defined as the time from randomization to the earlier of the date of study treatment discontinuation or death.
  • Duration of Response (DoR) [ Time Frame: Maximum of 45 Months ]
    Duration of response is the time from the first documentation of complete response (CR) or partial response (PR) until the date of progression or death, or the last evaluable RECIST assessment for participants that do not progress or progress after 2 missed assessments. Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria was used to assess participant response to treatment.
  • Time to Response (TTR) [ Time Frame: Maximum of 45 Months ]
    TTR was defined as the time from randomization until the date of first documented response by Blinded independent central review (BICR) assessment.
  • Mean Change From Baseline In Trial Outcome Index (TOI) Score [ Time Frame: Baseline (Day 1) to Week 48 (±1 week) ]
    The TOI score was derived from the sum of the scores of the 25 items included in the physical well-being (7 items), functional well-being (7 items), and additional concerns ovarian cancer subscale (11 items) of the FACT-O questionnaire Version 4. A negative change in score from baseline indicated a worsening in symptoms.
  • Number of Participants Who Show an Improvement in TOI Score [ Time Frame: Baseline (Day 1) to Week 48 (±1 week) ]
    The TOI score was derived from the sum of the scores of the 25 items included in the physical well-being (7 items), functional well-being (7 items), and additional concerns ovarian cancer subscale (11 items) of the FACT-O questionnaire Version 4. TOI score ranges from 0 to 100, a higher score indicates a higher health-related quality of life (HRQoL). A change in at least 10 points was considered clinically relevant.
  • Objective Response Rate (ORR) in Breast Cancer Susceptibility (BRCA) Gene Population by Blinded Independent Central Review (BICR) [ Time Frame: Maximum of 45 Months ]
    BRCA gene population includes participants identified as having a deleterious or suspected deleterious variant in either of the BRCA genes using variants identified with current and future BRCA mutation assays (eg, gene sequencing and large rearrangement analysis). The number of participants with complete or partial response per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria. Partial response is declared when there is a decrease in sum of target disease ≥ 30%. Complete response is declared when all lesions have disappeared or all lesions have disappeared and all nodal disease is < 10 mm each.
  • Number of Participants Who Experienced Disease Progression or Death in BRCA Gene Population by Blinded Independent Central Review (BICR) [ Time Frame: Maximum of 45 Months ]
    BRCA gene population includes participants identified as having a deleterious or suspected deleterious variant in either of the BRCA genes using variants identified with current and future BRCA mutation assays (eg, gene sequencing and large rearrangement analysis). Progressive disease was defined as at least 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
  • Number of Participants Who Experienced Second Progression or Death (PFS2) in BRCA Gene Population [ Time Frame: Maximum of 45 Months ]
    BRCA gene population includes participants identified as having a deleterious or suspected deleterious variant in either of the BRCA genes using variants identified with current and future BRCA mutation assays (eg, gene sequencing and large rearrangement analysis).
  • Overall Survival (OS) in BRCA Gene Population [ Time Frame: Maximum of 45 Months ]
    BRCA gene population includes participants identified as having a deleterious or suspected deleterious variant in either of the BRCA genes using variants identified with current and future BRCA mutation assays (eg, gene sequencing and large rearrangement analysis). OS in BRCA gene population was measured by the number of participants who died due to any cause.
  • Number of Participants Who Discontinued Study Treatment or Died in BRCA Gene Population [ Time Frame: Maximum of 45 Months ]
    BRCA gene population includes participants identified as having a deleterious or suspected deleterious variant in either of the BRCA genes using variants identified with current and future BRCA mutation assays (eg, gene sequencing and large rearrangement analysis).
  • Number of Participants Who Received Subsequent Chemotherapy or Died in BRCA Gene Population [ Time Frame: Maximum of 45 Months ]
    BRCA gene population includes participants identified as having a deleterious or suspected deleterious variant in either of the BRCA genes using variants identified with current and future BRCA mutation assays (eg, gene sequencing and large rearrangement analysis).
  • Number of Participants Who Received Second Subsequent Chemotherapy or Died in BRCA Gene Population [ Time Frame: Maximum of 45 Months ]
    BRCA gene population includes participants identified as having a deleterious or suspected deleterious variant in either of the BRCA genes using variants identified with current and future BRCA mutation assays (eg, gene sequencing and large rearrangement analysis).
  • Geometric Mean Plasma Concentration of Olaparib [ Time Frame: Day 1, 1 hour post-dose and Day 29 pre-dose ]
  • Number of Participants Who Experience at Least One Adverse Event (AE) [ Time Frame: Maximum of 45 Months ]
    An AE is the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 31, 2014)
  • Efficacy of olaparib vs. physician's choice single agent chemotherapy by assessment of Overall Survival (OS) [ Time Frame: Up to 60 months ]
    To determine the efficacy of olaparib vs. Physician's choice single agent chemotherapy by assessment of OS
  • Efficacy in patients following platinum based chemotherapy by assessment of time from randomisation to second progression [ Time Frame: From date of randomization until the date of second documented progression or date of death from any cause, whichever came first, assessed up to 60 months ]
    To determine the efficacy of olaparib vs. Physician's choice single agent chemotherapy by assessment of time from randomisation up to second progression
  • Efficacy in patients following platinum based chemotherapy by assessment of time to earliest progression by Cancer Antigen (CA-125) or death [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months ]
    To determine the efficacy of olaparib vs. Physician's choice single agent chemotherapy by assessment of time to earliest progression by CA-125 or death.
  • Time to deterioration of Health-Related Quality of Life (HRQoL) as assessed by trial outcome index (TOI) and the Functional Assessment of Cancer Therapy - Ovarian (FACT-O) [ Time Frame: Up to 48 weeks ]
    To determine the effects of olaparib vs. Physician's choice single agent chemotherapy by assessment of HRQoL as measured by TOI and FACT-O
  • Efficacy in patients with a deleterious or suspected deleterious variant in either of the BRCA genes by assessment of PFS. [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months ]
    To determine efficacy of olaparib in patients identified as having a deleterious or suspected deleterious variant in either of the BRCA genes using variants identified with current and future BRCA mutation assays (gene sequencing and large rearrangement analysis).
  • Efficacy of olaparib by time to first subsequent therapy or death (TFST). [ Time Frame: From date of randomization until the date of first subsequent therapy or death assessed up to 60 months ]
    To determine the efficacy of olaparib vs. Physician's choice single agent chemotherapy by assessment of time from randomisation to first subsequent therapy or death (TFST).
  • Efficacy of olaparib by time to second subsequent therapy or death (TSST). [ Time Frame: From date of randomization until the date of second subsequent therapy or death assessed up to 60 months ]
    To determine the efficacy of olaparib vs. Physician's choice single agent chemotherapy by assessment of time from randomisation to second subsequent therapy or death (TSST).
  • Efficacy of olaparib by time from randomisation to study treatment discontinuation or death (TDT). [ Time Frame: From date of randomization until the date of study treatment discontinuation or death assessed up to 60 months ]
    To determine the efficacy of olaparib vs. Physician's choice single agent chemotherapy by assessment of time from randomisation to study treatment discontinuation or death (TDT).
  • Safety and tolerability of olaparib by assessment of the number of Adverse Events (AEs). [ Time Frame: Up to 30 days post-treatment for up to 60 months ]
    To assess the safety and tolerability of olaparib maintenance monotherapy
  • Safety and tolerability of olaparib by review of laboratory parameters, ECG and vital signs [ Time Frame: Until study treatment discontinuation up to 60 months ]
    To assess the safety and tolerability of olaparib maintenance monotherapy
  • Efficacy in patients following platinum based chemotherapy by assessment of time to earliest progression by RECIST or death [ Time Frame: Radiological assessments will be scheduled every 8 weeks (+/- 1 week) from randomisation for 48 weeks and every 12 weeks (+/- 1 week) thereafter until objective disease progression. ]
    To determine the efficacy of olaparib vs. Physician's choice single agent chemotherapy by assessment of time to earliest progression by RECIST or death.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Olaparib Treatment in Relapsed Germline Breast Cancer Susceptibility Gene (BRCA) Mutated Ovarian Cancer Patients Who Have Progressed at Least 6 Months After Last Platinum Treatment and Have Received at Least 2 Prior Platinum Treatments
Official Title  ICMJE A Phase III, Open Label, Randomised, Controlled, Multi-centre Study to Assess the Efficacy and Safety of Olaparib Monotherapy Versus Physician's Choice Single Agent Chemotherapy in the Treatment of Platinum Sensitive Relapsed Ovarian Cancer in Patients Carrying Germline BRCA1/2 Mutations.
Brief Summary Comparison of olaparib vs. physician's choice of single agent standard of care non-platinum based chemotherapy in patients with germline Breast Cancer susceptibility gene (gBRCA) mutated ovarian cancer who have progressed at least 6 months after the last platinum based chemotherapy. Patient should have received at least 2 prior lines of platinum based chemotherapy. The aim of the study is to assess the efficacy and safety of olaparib tablets.
Detailed Description This open label, randomised, controlled, multi-centre study will assess the efficacy and safety of single agent olaparib vs. standard of care, based on physician's choice of single agent chemotherapy ( i.e paclitaxel, or topotecan, or pegylated liposomal doxorubicin, or gemcitabine) in platinum sensitive or partially platinum sensitive relapsed ovarian cancer patients who carry germline deleterious or suspected deleterious BRCA mutation and who have received at least 2 prior lines of platinum based chemotherapy. Patients are eligible to undergo BRCA testing even if they have not yet had recurrence or progression of disease >6 months (>/=183 days) after completion of their last platinum therapy.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Relapsed Ovarian Cancer, BRCA Mutation, Platinum Sensitivity
Intervention  ICMJE
  • Drug: OLAPARIB
    300 mg olaparib tablets taken orally twice daily. All patients should continue to receive study treatment until objective radiological disease progression as per RECIST 1.1 as assessed by the investigator or the patient experiences unacceptable toxicity or they meet any other discontinuation criteria.
  • Drug: Single agent chemotherapy
    Treatment of relapsed disease with single agent chemotherapy based on physician's choice of weekly paclitaxel, topotecan, pegylated liposomal doxorubicin, or gemcitabine. All patients should continue to receive study treatment until objective radiological disease progression as per RECIST 1.1 as assessed by the investigator or the patient experiences unacceptable toxicity or they meet any other discontinuation criteria
Study Arms  ICMJE
  • Experimental: 1/OLAPARIB
    olaparib 300mg oral tablets; twice daily
    Intervention: Drug: OLAPARIB
  • Active Comparator: 2/CHEMOTHERAPY
    Physician's choice single agent chemotherapy
    Intervention: Drug: Single agent chemotherapy
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: June 28, 2018)
266
Original Estimated Enrollment  ICMJE
 (submitted: October 31, 2014)
411
Estimated Study Completion Date  ICMJE May 31, 2021
Actual Primary Completion Date October 10, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients must be ≥ 18 years of age
  • Patients with histologically diagnosed relapsed high grade serous ovarian cancer (including primary peritoneal and/or fallopian tube cancer) or high grade endometrioid cancer. Patients are eligible to undergo BRCA testing even if they have not yet had recurrence or progression of disease >6 months (>/=183 days) after completion of their last platinum therapy.
  • Documented germline mutation in Breast Cancer susceptibility genes: BRCA1 and/or BRCA2 that is predicted to be deleterious or suspected deleterious (known or predicted to be detrimental/lead to loss of function)
  • At least one lesion that can be accurately assessed at baseline by CT/MRI and is suitable for repeated assessment.
  • Patients must have received at least 2 prior platinum based lines of chemotherapy - Patients must be partially platinum sensitive or platinum sensitive
  • Patients must be suitable to start treatment with single agent chemotherapy based on physician's choice
  • Patients must have normal organ and bone marrow function measured within 28 days of randomisation,
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Patients must have a life expectancy ≥ 16 weeks
  • Formalin fixed, paraffin embedded tumour sample from the primary or recurrent cancer must be available for central testing.

Exclusion Criteria:

  • BRCA 1 and/or BRCA2 mutations that are considered to be non detrimental
  • Exposure to any investigational product within 30 days or 5 half lives (whichever is longer) prior to randomisation
  • Any previous treatment with a Polyadenosine 5'diphosphoribose polymerisation (PARP) inhibitor, including olaparib.
  • Patients who have platinum resistant or refractory disease
  • Patients receiving any systemic chemotherapy within 3 weeks prior to first dose of study treatment
  • Previous single agent exposure to the selected chemotherapy regimen for randomisation. - Prior malignancy in the last 5 years, unless curatively treated and recurrence free (few exceptions apply).
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years to 130 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Mexico,   Argentina,   Belgium,   Brazil,   Canada,   Czechia,   Hungary,   Israel,   Italy,   Korea, Republic of,   Poland,   Spain,   United States
Removed Location Countries Czech Republic,   United Kingdom
 
Administrative Information
NCT Number  ICMJE NCT02282020
Other Study ID Numbers  ICMJE D0816C00010
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party AstraZeneca
Study Sponsor  ICMJE AstraZeneca
Collaborators  ICMJE
  • Myriad Genetic Laboratories, Inc.
  • Merck Sharp & Dohme Corp.
Investigators  ICMJE
Principal Investigator: Richard T Penson, Associate Prof. of Medicine Harvard Medical School
PRS Account AstraZeneca
Verification Date November 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP